The purpose of this project is to investigate the role of the central nervous system in regulating the mobilization of fuels to meet various physiologic needs such as fasting, exercise and stress and in regulating storage of fuels through control of feeding behavior. Mapping of central integrative areas will be done and assessment of efferent pathways and of humoral signals and neural inputs into the CNS based system for metabolic control will be investigated. Studies will be done in conscious primates (baboons, rhesus). Measurements of circulating fuels and hormones are made during changes in feeding schedule, infusion of potential humoral signals, after placement of discrete surgical or pharmacological lesions in the diencephalon, microinfusion of biogenic amines or other pharmacologic and endocrine agents into hypothalamic tissue or third brain ventricle. Mechanisms for possible chemoreceptor function will be investigated in rat hypothalamic tissues in vitro. Local uptake of circulating fuels and hormones into the hypothalamic areas concerned with metabolic regulations will also be studied in the rat. The physiologic role of somatostatin as a potential regulator of the endocrine pancreas will be studied in primates. Somatostatin will be used as a tool to investigate the role of glucagon and insulin in regulation of fuel mobilization in fasting primates. The recently discovered oscillations of glucose, insulin and glucagon in fasting rhesus monkeys will be investigated as to its site of origin and physiologic meaning. The functioning of CNS based metabolic controls in related human diseases (diabetes, obesity, atherosclerosis) will be investigated once the normal physiology has been characterized in subhuman primates.